Device and method for creating spherical particles of uniform size

ABSTRACT

Spherical particles having a size on the order of 0.1 to 100 microns in size are created by systems and devices of several types. The device includes a source of a stream of gas which is forced through a liquid held under pressure in a pressure chamber with an exit opening therein. The stream of gas surrounded by the liquid in the pressure chamber flows out of an exit orifice of the chamber into a liquid thereby creating a monodispersion of bubbles with substantially uniform diameter. The bubbles are small in size and produced with a relatively small amount of energy relative to comparable systems. Small particles of liquid may also be produced. Applications of the technology range from oxygenating sewage with monodispersions of bubbles to inhalation therapy with monodisperse aerosol dispersions of pharmaceutically active drugs.

FIELD OF THE INVENTION

[0001] The invention relates generally to the field of small particleformation and more specifically to fields where (1) it is important tocreate solid particles, liquid particles or gas bubbles which are verysmall and uniform in size and/or (2) it is important to avoid nozzleclogging when small nozzle openings are used to expel a fluid over along period of time.

BACKGROUND OF THE INVENTION

[0002] Monodispersed sprays of droplets of micrometric size haveattracted the interest of scientist and engineers because of theirpotential applications in many fields of science and technology.Recently, the possibility of getting medicines into patients viapulmonary inhalation is being actively investigated by pharmaceuticalcompanies around the world R. F. Service (1997), “Drug Delivery Takes aDeep Breath,” Science 277:1199-1200. Classifying a polydispersed aerosol(for example, by using a differential mobility analyzer, B. Y. Liu etal. (1974), “A Submicron Standard and the Primary Absolute Calibrationof the Condensation Nuclei Counter,” J. Coloid Interface Sci. 47:155-171or breakup process of Rayleigh's type of a capillary microjet LordRayleigh (1879), “On the instability of Jets,” Proc. London Math. Soc.10:4-13, are the current methods to produce the monodispersed aerosolsof micrometric droplets needed for such applications. The substantialloss of the aerosol sample during the classification process canseverely limit the use of this technique for some applications. On theother hand, although in the capillary break up the size distribution ofthe droplets can be very narrow, the diameter of the droplets isdetermined by the jet diameter (approximately twice the jet diameter).Therefore, the generation and control of capillary microjets areessential to the production of sprays of micrometric droplets with verynarrow size distribution.

[0003] Capillary microjets with diameters ranging from tens ofnanometers to hundred of micrometers are successfully generated byemploying high electrical fields (several kV) to form the well-knowncone-jet electrospray. Theoretical and experimental results andnumerical calculations on electrosprays can be obtained from M. Cloupeanet al. (1989), “Electrostatic Spraying of Liquids in Cone Jet Mode,” J.Electrostat 22:135-159, Fernández de la Mora et al. (1994), “The CurrentTransmitted through an Electrified Conical Meniscus,” J. Fluid Mech.260:155-184 and Loscertales (1994), A. M. Gañán-Calvo et al. (1997),“Current and Droplet Size in the Electrospraying of Liquids: ScalingLaws,” J. Aerosol Sci. 28:249-275, Hartman et al. (1997),“Electrohydrodynamic Atomization in the Cone-Jet Mode,” Paper presentedat the ESF Workshop on Electrospray, Sevilla, Feb.28-Mar. 1, 1997 amongothers [see also the papers contained in the Special Issue forElectrosprays (1994)]. In the electrospray technique the liquid to beatomized is slowly injected through a capillary electrified needle. Fora certain range of values of the applied voltage and flow rate an almostconical meniscus is formed at the needle's exit from whose vertex a verythin, charged jet is issued. The jet breaks up into a fine aerosol ofhigh charged droplets characterized by a very narrow droplet sizedistribution. Alternatively, the use of purely mechanical means toproduce capillary microjets is limited in most of applications forseveral reasons: the high-pressure values required to inject a liquidthrough a very narrow tube (typical diameters of the order of fewmicrometers) and the easy clogging of such narrow tubes due toimpurities in the liquid.

[0004] The present invention provides a new technique for generatingsteady microcapillary jets exclusively based on mechanical means whichdoes not present the above inconveniences and can compete advantageouslywith electrospray atomizers. The jet diameters produced with thistechnique can be easily controlled and range from below one micrometerto several tens of micrometers.

SUMMARY OF THE INVENTION

[0005] Spherical particles of liquid in the form of a monodispersion aswell as spherical particles of bubbles in the form of a monodispersionare disclosed wherein the particles have a size on the order of 0.1 to100 microns. The particles are created by various types of systems anddevices disclosed herein. The device includes a primary source of astream of liquid or gas which is forced through, respectively, a gas orliquid held under pressure in a pressure chamber. The pressure chamberhas an exit opening through which the stream is allowed to flowsurrounded by the surrounding gas or liquid. As the stream flows towardthe exit opening it forms a stable capillary microjet which jetdisassociates upon exiting the chamber: When certain parameters arecorrectly chosen the particles or bubbles formed are all substantiallyuniform in size with a very small degree of deviation, e.g., ±3% to±10%. The particles and bubbles are produced using a relatively smallamount of energy compared with the amount of energy used to produce suchin comparable systems. Small particles of liquid may be used in avariety of applications including fuel injection engines and theproduction of aerosols for the delivery of drugs by inhalation. Smallbubbles may be used for a variety of uses including decontamination ofgases and oxygenation of sewage or water in which fish or other plant oranimal life is present and in need of oxygen.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006]FIG. 1 is a schematic view showing the basic components of oneembodiment of the invention with a cylindrical feeding needle as asource of formulation.

[0007]FIG. 2 is a schematic view of another embodiment of the inventionwith two concentric tubes as a source of formulation.

[0008]FIG. 3 is a schematic view of yet another embodiment showing awedge-shaped planar source of formulation. FIG. 3a illustrates across-sectional side view of the planar feeding source and theinteraction of the fluids. FIG. 3b show a frontal view of the openingsin the pressure chamber, with the multiple openings through which theatomizate exits the device. FIG. 3c illustrates the channels that areoptionally formed within the planar feeding member. The channels arealigned with the openings in the pressure chamber.

[0009]FIG. 4 is a schematic view of a stable capillary microjet beingformed and flowing through an exit opening to thereafter form amonodisperse aerosol.

[0010]FIG. 5 is a graph of data where 350 measured values of d_(j)/d_(o)versus Q/Q_(o) are plotted.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0011] Before the present aerosol device and method are described, it isto be understood that this invention is not limited to the particularcomponents and steps described, as such may, of course, vary. It is alsoto be understood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present invention will be limited onlyby the appended claims.

[0012] It must be noted that as used herein and in the appended claims,the singular forms “a”, “and,” and “the” include plural referents unlessthe context clearly dictates otherwise. Thus, for example, reference to“a particle” includes a plurality of particles and reference to “afluid” includes reference to a mixture of fluids, and equivalentsthereof known to those skilled in the art, and so forth.

[0013] Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs. Although any methodsand materials similar or equivalent to those described herein can beused in the practice or testing of the present invention, the preferredmethods and materials are now described. All publications mentionedherein are incorporated herein by reference to disclose and describe themethods and/or materials in connection with which the publications arecited.

[0014] The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

DEVICE IN GENERAL

[0015] Different embodiments are shown and described herein (see FIGS.1, 2 and 3) which could be used in producing the stable capillarymicrojet and/or a dispersion of particles which are substantiallyuniform in size. Although various embodiments are part of the invention,they are merely provided as exemplary devices which can be used toconvey the essence of the invention, which is the formation of a stablecapillary microjet and/or uniform dispersion of particles.

[0016] A basic device comprises (1) a means for supplying a first fluidand (2) a pressure chamber supplied with a second fluid which flows outof an exit opening in the pressure chamber. The exit opening of thepressure chamber is aligned with the flow path of the means forsupplying the first fluid. The embodiments of FIGS. 1, 2 and 3 clearlyshow that there can be a variety of different means for supplying thefirst fluid. Other means for supplying a first fluid flow stream willoccur to those skilled in the art upon reading this disclosure.

[0017] Further, other configurations for forming the pressure chamberaround the means for supplying the first fluid will occur to thoseskilled in the art upon reading this disclosure. Such other embodimentsare intended to be encompassed by the present invention provided thebasic conceptual results disclosed here are obtained, i.e. a stablecapillary microjet is formed and/or a dispersion of particle highlyuniform in size is formed. Further description provided below shows thata stable microjet can be obtained when parameters are adjusted to obtaina Weber number of 1 or more but the disassociation of that microjet willnot provide a desired monodispersion unless the parameters are adjustedso that the Weber number is less than 40.

[0018] To simplify the description of the invention, the means forsupplying a first fluid is often referred to as a cylindrical tube (seeFIG. 1) and the first fluid is generally referred to as a liquid. Theliquid can be any liquid depending on the overall device which theinvention is used within. For example, the liquid could be a liquidformulation of a pharmaceutically active drug used to create an aerosolfor inhalation or, alternatively, it could be a hydrocarbon fuel used inconnection with a fuel injector for use on an internal combustion engineor heater or other device which burns hydrocarbon fuel. Further, forpurposes of simplicity, the second fluid is generally described hereinas being a gas and that gas is often preferably air. However, the firstfluid may be a gas and second fluid a liquid or both fluids may beliquid provided the first and second fluid are sufficiently differentfrom each other (immiscible) so as to allow for the formation of astable microjet of the first fluid moving from the supply means to anexit port of the pressure chamber. Notwithstanding these differentcombinations of gas-liquid, liquid-gas, and liquid-liquid, the inventionis generally described with a liquid formulation being expelled from thesupply means and forming a stable microjet due to interaction withsurrounding air flow focusing the microjet to flow out of an exit of thepressure chamber.

[0019] Formation of the microjet and its acceleration and ultimateparticle formation are based on the abrupt pressure drop associated withthe steep acceleration experienced by the liquid on passing through anexit orifice of the pressure chamber which holds the second fluid (i.e.the gas). On leaving the chamber the flow undergoes a large pressuredifference between the liquid and the gas, which in turn produces ahighly curved zone on the liquid surface near the exit port of thepressure chamber and in the formation of a cuspidal point from which asteady microjet flows, provided the amount of the liquid withdrawnthrough the exit port of the pressure chamber is replenished. Thus, inthe same way that a glass lens or a lens of the eye focuses light to agiven point, the flow of the gas surrounds and focuses the liquid into astable microjet. The focusing effect of the surrounding flow of gascreates a stream of liquid which is substantially smaller in diameterthan the diameter of the exit orifice of the pressure chamber. Thisallows liquid to flow out of the pressure chamber orifice withouttouching the orifice, providing advantages including (1) clogging of theexit orifice is virtually eliminated, (2) contamination of flow due tocontact with substances (e.g. bacteria or particulate residue) on theorifice opening is virtually eliminated, and (3) the diameter of thestream and the resulting particles are smaller than the diameter of theexit orifice of the chamber. This is particularly desirable because itis difficult to precisely engineer holes which are very small indiameter. Further, in the absence of the focusing effect (and formationa stable microjet) flow of liquid out of an opening will result inparticles which have about twice the diameter of the exit opening. Anadditional advantage is that the particles are not prone toagglomeration following exit from the chamber.

[0020] These advantages are all obtained with a system which uses a verysmall amount of energy as compared to other systems for creating eitheraerosolized particles of liquid in a gas or a monodispersion of bubblesin a liquid. More specifically, a given ideal minimum amount of energyis needed to move a stream of gas through a liquid or a stream of liquidthrough a gas. Further energy is needed (based on characteristics suchas surface tensions) to form small spherical particles or bubbles. Byusing methodology disclosed here a supercritical flow is obtainedcreating a stable capillary microjet. These characteristics move theflow stream and create the particles or bubbles using an amount ofenergy which is substantially closer to the minimum amount of energyrequired in an ideal system, i.e. it is closer to the ideal minimumamount of energy needed in other systems for obtaining such results.This is particularly important in some applications. For example, totreat sewage large amount of gas (air or oxygen) must be forced into thesewage to oxygenate the water. The smaller the bubbles and the greaterthe number of bubbles the more energy that is required. However, smallerbubbles present a greater surface area to the water resulting in greaterdiffusion of oxygen into the water. Further, smaller bubbles rise lessquickly and thereby provide contact between the air and water for agreater period of time—further enhancing the oxygenation of the water.

[0021] The description provided here generally indicates that the fluidleaves the pressure chamber through an exit orifice surrounded by thegas and thereafter enters into a gaseous surrounding environment whichmay be air held at normal atmospheric pressure, or, alternatively, thegas (heated pressurized air) inside an internal combustion engine.However, when the first fluid is a gas and the second fluid is a liquidthe fluid present outside of the chamber may also be a liquid. Thisconfiguration is particularly useful when it is necessary to create verysmall highly uniform bubbles which are moved into a liquid surroundingexit opening of the pressure chamber. The need for the formation of verysmall highly uniform bubbles into a gas occurs in a variety of differentindustrial applications. For example, water needs to be oxygenated in avariety of situations including small at home fish tanks and largevolume fisheries. The additional oxygen can aid the rate of growth ofthe fish and thereby improve production for the fishery. In theembodiment described above, oxygen or air bubbles can be forced intoliquid sewage in order to aid in treatment. In yet another applicationof the invention, contaminated gases such as a gas contaminated withtoxins such as a radioactive material can be formed into small uniformedbubbles and blown into a liquid where the contamination in the gas willdiffuse into the liquid, thereby cleaning the gas. The liquid will, ofcourse, occupy substantially less volume and therefore be substantiallyeasier to dispose of than contaminated toxic gas.

[0022] Those skilled in the art will recognize that variations on thedifferent embodiments disclosed below will be useful in obtainingparticularly preferred results. Specific embodiments of devices are nowdescribed.

EMBODIMENT OF FIG. 1

[0023] A first embodiment of the invention where the supply means is acylindrical feeding needle supplying liquid into a pressurized chamberof gas is described below with reference to FIG. 1.

[0024] The components of the embodiment of FIG. I are as follows:

[0025]1. Feeding needle—also referred to generally as a fluid source anda tube.

[0026]2. End of the feeding needle used to insert the liquid to beatomized.

[0027]3. Pressure chamber.

[0028]4. Orifice used as gas inlet.

[0029]5. End of the feeding needle used to evacuate the liquid to beatomized.

[0030]6. Orifice through which withdrawal takes place.

[0031]7. Atomizate (spray)—also referred to as aerosol.

[0032] D₀ diameter of the feeding needle; d₀=diameter of the orificethrough which the microjet is passed; e=axial length of the orificethrough which withdrawal takes place; H=distance from the feeding needleto the microjet outlet; P₀=pressure inside the chamber;P_(α)=atmospheric pressure.

[0033] Although the device can be configured in a variety of designs,the different designs will all include the essential components shown inFIG. 1 or components which perform an equivalent function and obtain thedesired results. Specifically, a device of the invention will becomprised of at least one source of a first fluid (e.g., a feedingneedle with an opening 2) into which a first fluid such as liquidflowable formulation can be fed and an exit opening 5 from which theformulation can be expelled. The feeding needle 1, or at least its exitopening 5, is encompassed by a pressure chamber 3. The chamber 3 hasinlet opening 4 which is used to feed a second fluid (e.g. a gas) intothe chamber 3 and an exit opening 6 through which gas from the pressurechamber and liquid formulation from the feeding needle 3 are expelled.When the first fluid is a liquid it is expelled into gas to create anaerosol. When the first fluid is a gas it is expelled into a liquid tocreate bubbles.

[0034] In FIG. 1, the feeding needle and pressure chamber are configuredto obtain a desired result of producing an aerosol wherein the particlesare small and uniform in size or bubbles which are small and uniform insize. The particles or bubbles have a size which is in a range of 0.1 to100 microns. The particles of any given aerosol or bubbles will all haveabout the same diameter with a relative standard deviation of ±10% to±30 % or more preferably ±3% to ±10%. Stating that particles of theaerosol have a particle diameter in a range of 1 to 5 microns does notmean that different particles will have different diameters and thatsome will have a diameter of 1 micron while others of 5 microns. Theparticles in a given aerosol will all (preferably about 90% or more)have the same diameter ±3% to ±30%. For example, the particles of agiven aerosol will have a diameter of 2 microns ±3% to ±10%. The samedeviations are also correct for the formation of bubbles.

[0035] Such a monodisperse aerosol is created using the components andconfiguration as described above. However, other components andconfigurations will occur to those skilled in the art. The object ofeach design will be to supply fluid so that it creates a stablecapillary microjet which is accelerated and stabilized by tangentialviscous stress exerted by the second fluid on the first fluid surface.The stable microjet created by the second fluid leaves the pressurizedarea (e.g., leaves the pressure chamber and exits the pressure chamberorifice) and splits into particles or bubbles which have the desiredsize and uniformity.

[0036] The parameter window used (i.e. the set of special values for theliquid properties, flow-rate used, feeding needle diameter, orificediameter, pressure ratio, etc.) should be large enough to be compatiblewith virtually any liquid (dynamic viscosities in the range from 10⁻⁴ to1 kg m⁻¹s⁻¹); in this way, the capillary microjet that emerges from theend of the feeding needle is absolutely stable and perturbationsproduced by breakage of the jet cannot travel upstream. Downstream, themicrojet splits into evenly shaped drops simply by effect of capillaryinstability (see, for example, Rayleigh, “On the instability of jets”,Proc. London Math. Soc., 4-13, 1878), similar in a manner to a laminarcapillary jet falling from a half-open tap.

[0037] When the stationary, steady interface is created, the capillaryjet that emerges from the end of the drop at the outlet of the feedingpoint is concentrically withdrawn into the nozzle. After the jet emergesfrom the drop, the liquid is accelerated by tangential sweeping forcesexerted by the gas stream flowing on its surface, which graduallydecreases the jet cross-section. Stated differently the gas flow acts asa lens and focuses and stabilizes the microjet as it moves toward andinto the exit orifice of the pressure chamber.

[0038] The forces exerted by the second fluid flow on the first fluidsurface should be steady enough to prevent irregular surfaceoscillations. Therefore, any turbulence in the gas motion should beavoided; even if the gas velocity is high, the characteristic size ofthe orifice should ensure that the gas motion is laminar (similar to theboundary layers formed on the jet and on the inner surface of the nozzleor hole).

STABLE CAPILLARY MICROJET

[0039]FIG. 4 illustrates the interaction of a liquid and a gas to formatomizate using the method of the invention. The feeding needle 60 has acircular exit opening 61 with an internal radius R₀ which feeds a liquid62 out of the end, forming a drop with a radius in the range of R₀ to R₀plus the thickness of the wall of the needle. The exiting liquid formsan infinite amount of liquid streamlines 63 that interact with thesurrounding gas to form a stable cusp at the interface 64 of the twofluids. The surrounding gas also forms an infinite number of gasstreamlines 65, which interact with the exiting liquid to create avirtual focusing funnel 66. The exiting liquid is focused by thefocusing funnel 66 resulting in a stable capillary microjet 67, whichremains stable until it exits the opening 68 of the pressure chamber 69.After exiting the pressure chamber, the microjet begins to break-up,forming monodispersed particles 70.

[0040] The gas flow, which affects the liquid withdrawal and itssubsequent acceleration after the jet is formed, should be very rapidbut also uniform in order to avoid perturbing the fragile capillaryinterface (the surface of the drop that emerges from the jet).

[0041] Liquid flows out of the end of a capillary tube and forms a smallliquid drop at the end. The tube has an internal radius R_(o). The drophas a radius in a range of from R_(o) to R_(o) plus the structuralthickness of the tube as the drop exits the tube, and thereafter thedrop narrows in circumference to a much smaller circumference as isshown in the expanded view of the tube (i.e. feeding needle) 5 as shownin FIGS. 1 and 4.

[0042] As illustrated in FIG. 4, the exit opening 61 of the capillarytube 60 is positioned close to an exit opening 68 in a planar surface ofa pressure chamber 69. The exit opening 68 has a minimum diameter D andis in a planar member with a thickness L. The diameter D is referred toas a minimum diameter because the opening may have a conicalconfiguration with the narrower end of the cone positioned closer to thesource of liquid flow. Thus, the exit opening may be a funnel-shapednozzle although other opening configurations are also possible, e.g. anhour glass configuration. Gas in the pressure chamber continuously flowsout of the exit opening. The flow of the gas causes the liquid dropexpelled from the tube to decrease in circumference as the liquid movesaway from the end of the tube in a direction toward the exit opening ofthe pressure chamber.

[0043] In actual use, it can be understood that the opening shape whichprovokes maximum gas acceleration (and consequently the most stable cuspand microjet with a given set of parameters) is a conically shapedopening in the pressure chamber. The conical opening is positioned withits narrower end toward the source of liquid flow.

[0044] The distance between the end 61 of the tube 60 and the beginningof the exit opening 68 is H. At this point it is noted that R₀, D, H andL are all preferably on the order of hundreds of microns. For example,R₀=400 μm, D=150 μm, H=1 mm, L=300 μm. However, each could be {fraction(1/100)} to 100× these sizes.

[0045] The end of the liquid stream develops a cusp-like shape at acritical distance from the exit opening 68 in the pressure chamber 69when the applied pressure drop ΔP_(g) across the exit opening 68overcomes the liquid-gas surface tension stresses γ/R* appearing at thepoint of maximum curvature—e.g. 1/R* from the exit opening.

[0046] A steady state is then established if the liquid flow rate Qejected from the drop cusp is steadily supplied from the capillary tube.This is the stable capillary cusp which is an essential characteristicof the invention needed to form the stable microjet. More particularly,a steady, thin liquid jet with a typical diameter d_(j) is smoothlyemitted from the stable cusp-like drop shape and this thin liquid jetextends over a distance in the range of microns to millimeters. Thelength of the stable microjet will vary from very short (e.g. 1 micron)to very long (e.g. 50 mm) with the length depending on the (1) flow-rateof the liquid and (2) the Reynolds number of the gas stream flowing outof the exit opening of the pressure chamber. The liquid jet is thestable capillary microjet obtained when supercritical flow is reached.This jet demonstrates a robust behavior provided that the pressure dropΔP_(g) applied to the gas is sufficiently large compared to the maximumsurface tension stress (on the order of γ/d_(j)) that act at theliquid-gas interface. The jet has a slightly parabolic axial velocityprofile which is, in large part, responsible for the stability of themicrojet. The stable microjet is formed without the need for otherforces, i.e. without adding force such as electrical forces on a chargedfluid. However, for some applications it is preferable to add charge toparticles, e.g. to cause the particles to adhere to a given surface. Theshaping of liquid exiting the capillary tube by the gas flow forming afocusing funnel creates a cusp-like meniscus resulting in the stablemicrojet. This is a fundamental characteristic of the invention.

[0047] The fluid stream flowing from the tube has substantially moredensity and develops substantially more inertia as compared to the gas,which has lower viscosity than the liquid. These characteristicscontribute to the formation of the stable capillary jet. The stablecapillary microjet is maintained stably for a significant distance inthe direction of flow away from the exit from the tube. The liquid is,at this point, undergoing “supercritical flow.” The microjet eventuallydestabilizes due to the effect of surface tension forces.Destabilization results from small natural perturbations movingdownstream, with the fastest growing perturbations being those whichgovern the break up of the microjet, eventually creating a monodisperse(a uniform sized) aerosol 70 as shown in FIG. 4.

[0048] The microjet, even as it initially destabilizes, passes out ofthe exit orifice of the pressure chamber without touching the peripheralsurface of the exit opening. This provides an important advantage of theinvention which is that the exit opening 68 (which could be referred toas a nozzle) will not clog from residue and/or deposits of the liquid.Clogging is a major problem with very small nozzles and is generallydealt with by cleaning or replacing the nozzle. When fluid contacts thesurfaces of a nozzle opening some fluid will remain in contact with thenozzle when the flow of fluid is shut off. The liquid remaining on thenozzle surface evaporates leaving a residue. After many uses over timethe residue builds up and clogging takes place. The present inventionsubstantially reduces or eliminates this clogging problem.

MATHEMATICS OF A STABLE MICROJET

[0049] Cylindrical coordinates (r,z) are chosen for making amathematical analysis of a stable microjet, i.e. liquid undergoing“supercritical flow.” The cusp-like meniscus formed by the liquid comingout of the tube is pulled toward the exit of the pressure chamber by apressure gradient created by the flow of gas.

[0050] The cusp-like meniscus formed at the tube's mouth is pulledtowards the hole by the pressure gradient created by the gas stream.From the cusp of this meniscus, a steady liquid thread with the shape ofradius r=ξ is withdrawn through the hole by the action of both thesuction effect due to ΔP_(g), and the tangential viscous stresses τ_(s)exerted by the gas on the jet's surface in the axial direction. Theaveraged momentum equation for this configuration may be written$\begin{matrix}{{{\frac{d}{d_{z}}\left\lbrack {P_{1} + \frac{\rho_{1}Q^{2}}{2\Pi^{2}\xi^{4}}} \right\rbrack} = \frac{2\quad \tau_{s}}{\xi}},} & (1)\end{matrix}$

[0051] where Q is the liquid flow rate upon exiting the feeding tube, P₁is the liquid pressure, and ρ₁ is the liquid density, assuming that theviscous extensional term is negligible compared to the kinetic energyterm, as will be subsequently justified. In addition, liquid evaporationeffects are neglected. The liquid pressure P₁ is given by the capillaryequation. $\begin{matrix}{P_{1} = {P_{g} + {\gamma/{\xi.}}}} & (2)\end{matrix}$

[0052] where γ is the liquid-gas surface tension. As shown in theExamples, the pressure drop ΔP_(g) is sufficiently large as compared tothe surface tension stress γ/ξ to justify neglecting the latter in theanalysis. This scenario holds for the whole range of flow rates in whichthe microjet is absolutely stable. In fact, it will be shown that, for agiven pressure drop ΔP_(g), the minimum liquid flow rate that can besprayed in steady jet conditions is achieved when the surface tensionstress γ/ξ is of the order of the kinetic energy of the liquidρ₁Q²/(2π²ξ⁴), since the surface tension acts like a “resistance” to themotion (it appears as a negative term in the right-hand side term of Eq.(1)). Thus, $\begin{matrix}{\left. Q_{\min} \right.\sim\left( \frac{\gamma \quad d_{j}^{3}}{\rho_{1}} \right)^{1/2}} & (3)\end{matrix}$

[0053] For sufficiently large flow rates Q compared to Q_(min), thesimplified averaged momentum equation in the axial direction can beexpressed as $\begin{matrix}{{{\frac{d}{d_{z}}\left( \frac{\rho_{1}Q^{2}}{2\Pi^{2}\xi^{4}} \right)} = {\frac{d\quad P_{g}}{d_{z}} + \frac{2\tau_{s}}{\xi}}},} & (4)\end{matrix}$

[0054] where one can identify the two driving forces for the liquid flowon the right-hand side. This equation can be integrated provided thefollowing simplification is made: if one uses a thin plate withthickness L of the order or smaller than the hole's diameter D (whichminimizes downstream perturbations in the gas flow), the pressuregradient up to the hole exit is on the average much larger than theviscous shear term 2τ_(s)/ξ owning to the surface stress. On the otherhand, the axial viscous term is of the order O[μ²Q/D²d_(j) ²], since thehole diameter D is actually the characteristic distance associated withthe gas flow at the hole's entrance in both the radial and axialdirections. This term is very small compared to the pressure gradient inreal situations, provided that ΔP_(g)>>μ²/D²ρ₁ (which holds, e.g., forliquids with viscosities as large as 100 cpoises, using hole diametersand pressure drops as small as D˜10 μm and ΔP_(g)>100 mbar). The neglectof all viscous terms in Eq. (4) is then justified. Notice that in thislimit on the liquid flow is quasi-isentropic in the average (the liquidalmost follows Bernoulli equation) as opposed to most micrometricextensional flows. Thus, integrating (4) from the stagnation regions ofboth fluids up to the exit, one obtains a simple and universalexpression for the jet diameter at the hole exit: $\begin{matrix}{{d_{j} \simeq {\left( \frac{8\rho_{1}}{\Pi^{2}\Delta \quad P_{g}} \right)^{1/4}Q^{1/2}}},} & (5)\end{matrix}$

[0055] which for a given pressure drop ΔP_(g) is in dependent ofgeometrical parameters (hole and tube diameters, tube-hole distance,etc.), liquid and gas viscosities, and liquid-gas surface tension. Thisdiameter remains almost constant up to the breakup point since the gaspressure after the exit remains constant.

MONODISPERSE PARTICLES

[0056] Above the stable microjet undergoing “supercritical flow” isdescribed and it can be seen how this aspect of the invention can bemade use of in a variety of industrial applications—particularly wherethe flow of liquid through small holes creates a clogging problem. Anequally important aspect of the invention is obtained after the microjetleaves the pressure chamber.

[0057] When the microjet exits the pressure chamber the liquid pressureP₁ becomes (like the gas pressure P_(g)) almost constant in the axialdirection, and the jet diameter remains almost constant up to the pointwhere it breaks up by capillary instability. Defining a Weber numberWe=(ρ_(g)ν_(g) ²d_(j))/γ≅2ΔP_(g)d_(j)/γ (where ν_(g) is the gas velocitymeasured at the orifice), below a certain experimental value We_(c)˜40the breakup mode is axisymmetric and the resulting droplet stream ischaracterized by its monodispersity provided that the fluctuations ofthe gas flow do not contribute to droplet coalescence (thesefluctuations occur when the gas stream reaches a fully developedturbulent profile around the liquid jet breakup region). Above thisWe_(c) value, sinuous nonaxisymmetric disturbances, coupled to theaxisymmetric ones, become apparent. For larger We numbers, the nonlineargrowth rate of the sinuous disturbances seems to overcome that of theaxisymmetric disturbances. The resulting spray shows significantpolydispersity in this case. Thus, it can be seen that by controllingparameters to keep the resulting Weber number to 40 or less, allows theparticles formed to be all substantially the same size. The sizevariation is about ±3% to ±30% and move preferably ±3% to ±10%. Theseparticles can have a desired size e.g. 0.1 microns to 50 microns.

[0058] The shed vorticity influences the breakup of the jet and thus theformation of the particles. Upstream from the hole exit, in theaccelerating region, the gas stream is laminar. Typical values of theReynolds number range from 500 to 6000 if a velocity of the order of thespeed of sound is taken as characteristic of the velocity of the gas.Downstream from the hole exit, the cylindrical mixing layer between thegas stream and the stagnant gas becomes unstable by the classicalKelvin-Helmholtz instability. The growth rate of the thickness of thislayer depends on the Reynolds number of the flow and ring vortices areformed at a frequency of the order of ν_(g)/D where D is the holediameter. Typical values of ν_(g) and D as those found in ourexperimental technique lead to frequencies or the order of MHZ which arecomparable to the frequency of drop production (of order of t_(b) ⁻¹).

[0059] Given the liquid flow rate and the hole diameter, a resonancefrequency which depends on the gas velocity (or pressure differencedriving the gas stream) can be adjusted (tuned) in such a way thatvortices act as a forcing system to excite perturbations of a determinedwavelength on the jet surface. Experimental results obtained clearlyillustrates the different degree of coupling between the two gas-liquidcoaxial jets. In one set of experimental results the particle sizes areshown to have a particle size of about 5.7 microns with a standarddeviation of 12%. This results when the velocity of the gas has beenproperly tuned to minimize the dispersion in the size of dropletsresulting from the jet breakup. In this case, the flow rate of theliquid jet and its diameter are 0.08 μl s⁻¹ and 3 μm, respectively. Datahave been collected using a MASTERSIZER from MALVERN Instruments. As thedegree of coupling decreases, perturbations at the jet surface ofdifferent wavelengths become excited and, as it can be observed from thesize distributions, the dispersion of the spray increases.

[0060] It is highly desirable in a number of different industrialapplications to have particles which are uniform in size or to createaerosols of liquid particles which are uniform in size. For example,particles of a liquid formation containing a pharmaceutically activedrug could be created and designed to have a diameter of about 2 microns±3%. These particles could be inhaled into the lungs of a patient forintrapulmonary drug delivery. Moreover, particle size can be adjusted totarget a particular area of the respiratory tract.

[0061] The gas flow should be laminar in order to avoid a turbulentregime—turbulent fluctuations in the gas flow which have a highfrequency and would perturb the liquid-gas interface. The Reynoldsnumbers reached at the orifice are${Re} = {\left. \frac{v_{g}d_{0}}{v_{g}} \right.\sim 4000}$

[0062] where ν_(g) is the kinematic viscosity of the gas. Even thoughthis number is quite high, there are large pressure gradients downstream(a highly convergent geometry), so that a turbulent regime is veryunlikely to develop.

[0063] The essential difference from existing pneumatic atomizers (whichpossess large Weber numbers) and the present invention is that the aimof the present invention is not to rupture the liquid-gas interface butthe opposite, i.e. to increase the stability of the interface until acapillary jet is obtained. The jet, which will be very thin provided thepressure drop resulting from withdrawal is high enough, splits intodrops the sizes of which are much more uniform than those resulting fromdisorderly breakage of the liquid-gas interface in existing pneumaticatomizers.

[0064] The proposed atomization system obviously requires delivery ofthe liquid to be atomized and the gas to be used in the resulting spray.Both should be fed at a rate ensuring that the system lies within thestable parameter window. Multiplexing is effective when the flow-ratesneeded exceed those on an individual cell. More specifically, aplurality of feeding sources or feeding needles may be used to increasethe rate at which aerosols are created. The flow-rates used should alsoensure the mass ratio between the flows is compatible with thespecifications of each application.

[0065] The gas and liquid can be dispensed by any type of continuousdelivery system (e.g. a compressor or a pressurized tank the former anda volumetric pump or a pressurized bottle the latter). If multiplexingis needed, the liquid flow-rate should be as uniform as possible amongcells; this may entail propulsion through several capillary needles,porous media or any other medium capable of distributing a uniform flowamong different feeding points.

[0066] Each individual atomization device should consist of a feedingpoint (a capillary needle, a point with an open microchannel, amicroprotuberance on a continuous edge, etc.) 0.002-2 mm (but,preferentially 0.01-0.4 mm) in diameter, where the drop emerging fromthe microjet can be anchored, and a small orifice 0.002-2 mm(preferentially 0.01-0.25 mm) in diameter facing the drop and separated0.01-2 mm (preferentially 0.2-0.5 mm) from the feeding point. Theorifice communicates the withdrawal gas around the drop, at an increasedpressure, with the zone where the atomizate is produced, at a decreasedpressure. The atomizer can be made from a variety of materials (metal,polymers, ceramics, glass).

[0067]FIG. 1 depicts a tested prototype where the liquid to be atomizedis inserted through one end of the system 2 and the propelling gas inintroduced via the special inlet 4 in the pressure chamber 3. Theprototype was tested at gas feeding rates from 100 to 2000 mBar abovethe atmospheric pressure P_(α) at which the atomized liquid wasdischarged. The whole enclosure around the feeding needle 1 was at apressure P₀>P_(α). The liquid feeding pressure, P_(l), should always beslightly higher than the gas propelling pressure, P_(o). Depending onthe pressure drop in the needle and the liquid feeding system, thepressure difference (P₁−P₀>0) and the flow-rate of the liquid to beatomized, Q, are linearly related provided the flow is laminar—which isindeed the case with this prototype. The critical dimensions are thedistance from the needle to the plate (H), the needle diameter (D₀), thediameter of the orifice through which the microjet 6 is discharged (d₀)and the axial length, e, of the orifice (i.e. the thickness of the platewhere the orifice is made). In this prototype, H was varied from 0.3 to0.7 mm on constancy of the distances (D₀=0.45 mm, d₀−0.2 mm) and e−0.5mm. The quality of the resulting spray 7 did not vary appreciably withchanges in H provided the operating regime (i.e. stationary drop andmicrojet) was maintained. However, the system stability suffered at thelonger H distances (about 0.7 mm). The other atomizer dimensions had noeffect on the spray or the prototype functioning provided the zonearound the needle (its diameter) was large enough relative to thefeeding needle.

WEBER NUMBER

[0068] Adjusting parameters to obtain a stable capillary microjet andcontrol its breakup into monodisperse particle is governed by the Webernumber and the liquid-to-gas velocity ratio or α which equal V₁/V_(g).The Weber number or “We” is defined by the following equation:${We} = \frac{\rho_{g}V_{g}^{2}d}{\gamma}$

[0069] wherein ν_(g) is the density of the gas, d is the diameter of thestable microjet, γ is the liquid-gas surface tension, and V_(g) ² is thevelocity of the gas squared.

[0070] When carrying out the invention the parameters should be adjustedso that the Weber number is greater than 1 in order to produce a stablecapillary microjet. However, to obtain a particle dispersion which ismonodisperse (i.e. each particle has the same size ±3 to ±30%) theparameters should be adjusted so that the Weber number is less than 40.The monodisperse aerosol is obtained with a Weber number in a range ofabout 1 to about 40 when the breaking time is sufficiently small toavoid non-symmetric perturbations. (1≦We≦40)

OHNESORGE NUMBER

[0071] A measure of the relative importance of viscosity on the jetbreakup can be estimated from the Ohnesorge number defined as the ratiobetween two characteristic times: the viscous time t_(v) and thebreaking time t_(b). The breaking time tb is given by [see Rayleigh(1878)] $\begin{matrix}{{\left. t_{b} \right.\sim\left( \frac{\rho_{l}d^{2}}{\gamma} \right)^{1/2}}.} & (2)\end{matrix}$

[0072] Perturbations on the jet surface are propagated inside by viscousdiffusion in times t_(ν) of the order of $\begin{matrix}{{{\left. t_{v} \right.\sim\rho_{l}}{d^{2}/\mu_{1}}},} & (3)\end{matrix}$

[0073] where μ₁ is the viscosity of the liquid. Then, the Ohnesorgenumber, Oh, results $\begin{matrix}{{Oh} = {\frac{\mu_{1}}{\left( {\rho_{l}\gamma \quad d} \right)^{1/2}}.}} & (4)\end{matrix}$

[0074] If this ratio is much smaller than unity viscosity plays noessential role in the phenomenon under consideration. Since the maximumvalue of the Ohnesorge number in actual experiments conducted is as lowas 3.7×10⁻², viscosity plays no essential role during the process of jetbreakup.

EMBODIMENT OF FIG. 2

[0075] A variety of configurations of components and types of fluidswill become apparent to those skilled in the art upon reading thisdisclosure. These configurations and fluids are encompassed by thepresent invention provided they can produce a stable capillary microjetof a first fluid from a source to an exit port of a pressure chambercontaining a second fluid. The stable microjet is formed by the firstfluid flowing from the feeding source to the exit port of the pressurechamber being accelerated and stabilized by tangential viscous stressexerted by the second fluid in the pressure chamber on the surface ofthe first fluid forming the microjet. The second fluid forms a focusingfunnel when a variety of parameters are correctly tuned or adjusted. Forexample, the speed, pressure, viscosity and miscibility of the first andsecond fluids are chosen to obtain the desired results of a stablemicrojet of the first fluid focused into the center of a funnel formedwith the second fluid. These results are also obtained by adjusting ortuning physical parameters of the device, including the size of theopening from which the first fluid flows, the size of the opening fromwhich both fluids exit, and the distance between these two openings.

[0076] The embodiment of FIG. 1 can, itself, be arranged in a variety ofconfigurations. Further, as indicated above, the embodiment may includea plurality of feeding needles. A plurality of feeding needles may beconfigured concentrically in a single construct, as shown in FIG. 2.

[0077] The components of the embodiment of FIG. 2 are as follows:

[0078]21. Feeding needle tube or source of fluid.

[0079]22. End of the feeding needle used to insert the liquids to beatomized.

[0080]23. Pressure chamber.

[0081]24. Orifice used as gas inlet.

[0082]25. End of the feeding needle used to evacuate the liquid to beatomized.

[0083]26. Orifice through which withdrawal takes place.

[0084]27. Atomizate (spray) or aerosol.

[0085]28. First liquid to be atomized (inner core of particle).

[0086]29. Second liquid to be atomized (outer coating of particle).

[0087]30. Gas for creation of microjet.

[0088]31. Internal tube of feeding needle.

[0089]32. External tube of feeding needle.

[0090] D=diameter of the feeding needle; d=diameter of the orificethrough which the microjet is passed; e=axial length of the orificethrough which withdrawal takes place; H=distance from the feeding needleto the microjet outlet; γ=surface tension; P₀=pressure inside thechamber; P₆₀=atmospheric pressure.

[0091] The embodiment of FIG. 2 is preferably used when attempting toform a spherical particle of one substance coated by another substance.The device of FIG. 2 is comprised of the same basic component as per thedevice of FIG. I and further includes a second feeding source 32 whichis positioned concentrically around the first cylindrical feeding source31. The second feeding source may be surrounded by one or moreadditional feeding sources with each concentrically positioned aroundthe preceding source. The outer coating may be used for a variety ofpurposes, including: coating particles to prevent small particles fromsticking together; to obtain a sustained release effect of the activecompound (e.g. a pharmaceutically active drug) inside, and/or to maskflavors; and to protect the stability of another compound (e.g. apharmaceutically active drug) contained therein.

[0092] The process is based on the microsuction which the liquid-gas orliquid-liquid interphase undergoes (if both are immiscible), when saidinterphase approaches a point beginning from which one of the fluids issuctioned off while the combined suction of the two fluids is produced.The interaction causes the fluid physically surrounded by the other toform a capillary microjet which finally breaks into spherical drops. Ifinstead of two fluids (gas-liquid), three or more are used that flow ina concentric manner by injection using concentric tubes, a capillary jetcomposed of two or more layers of different fluids is formed which, whenit breaks, gives rise to the formation of spheres composed of severalapproximately concentric spherical layers of different fluids. The sizeof the outer sphere (its thickness) and the size of the inner sphere(its volume) can be precisely adjusted. This can allow the manufactureof coated particles for a variety of end uses. For example the thicknessof the coating can be varied in different manufacturing events to obtaincoated particles which have gradually decreasing thicknesses to obtain acontrolled release effect of the contents, e.g. a pharmaceuticallyactive drug. The coating could merely prevent the particles fromdegrading, reacting, or sticking together.

[0093] The method is based on the breaking of a capillary microjetcomposed of a nucleus of one liquid or gas and surrounded by another orother liquids and gases which are in a concentric manner injected by aspecial injection head, in such a way that they form a stable capillarymicrojet and that they do not mix by diffusion during the time betweenwhen the microjet is formed and when it is broken. When the capillarymicrojet is broken into spherical drops under the proper operatingconditions, which will be described in detail below, these drops exhibita spherical nucleus, the size and eccentricity of which can becontrolled.

[0094] In the case of spheres containing two materials, the injectionhead 25 consists of two concentric tubes with an external diameter onthe order of one millimeter. Through the internal tube 31 is injectedthe material that will constitute the nucleus of the microsphere, whilebetween the internal tube 31 and the external tube 32 the coating isinjected. The fluid of the external tube 32 joins with the fluid of tube31 as the fluids exit the feeding needle, and the fluids (normallyliquids) thus injected are accelerated by a stream of gas that passesthrough a small orifice 24 facing the end of the injection tubes. Whenthe drop in pressure across the orifice 24 is sufficient, the liquidsform a completely stationary capillary microjet, if the quantities ofliquids that are injected are stationary. This microjet does not touchthe walls of the orifice, but passes through it wrapped in the stream ofgas or funnel formed by gas from the tube 32. Because the funnel of gasfocuses the liquid, the size of the exit orifice 26 does not dictate thesize of the particles formed.

[0095] When the parameters are correctly adjusted, the movement of theliquid is uniform at the exit of the orifice 26 and the viscosity forcesare sufficiently small so as not to alter either the flow or theproperties of the liquids; for example, if there are biochemicalmolecular specimens having a certain complexity and fragility, theviscous forces that would appear in association with the flow through amicro-orifice might degrade these substances.

[0096]FIG. 2 shows a simplified diagram of the feeding needle 21, whichis comprised of the concentric tubes 30, 31 through the internal andexternal flows of the fluids 28, 29 that are going to compose themicrospheres comprised of two immiscible fluids. The difference inpressures P₀−P_(α)(P₀>P_(α)) through the orifice 26 establishes a flowof gas present in the chamber 23 and which is going to surround themicrojet at its exit. The same pressure gradient that moves the gas isthe one that moves the microjet in an axial direction through the hole26, provided that the difference in pressures P₀−P₆₀ is sufficientlygreat in comparison with the forces of surface tension, which create anadverse gradient in the direction of the movement.

[0097] There are two limitations for the minimum sizes of the inside andoutside jets that are dependent (a) on the surface tensions γ1 of theoutside liquid 29 with the gas 30 and γ2 of the outside liquid 29 withthe inside liquid 28, and (b) on the difference in pressures ΔP=P₀−P_(α)through the orifice 26. In the first place, the jump in pressures ΔPmust be sufficiently great so that the adverse effects of the surfacetension are minimized. This, however, is attained for very modestpressure increases: for example, for a 10 micron jet of a liquid havinga surface tension of 0.05 N/m (tap water), the necessary minimum jump inpressure is in the order of 0.05 (N/m)/0.00001 m=ΔP=50 mBar. But, inaddition, the breakage of the microjet must be regular andaxilsymmetric, so that the drops will have a uniform size, while theextra pressure ΔP cannot be greater than a certain value that isdependent on the surface tension of the outside liquid with the gas γ1and on the outside diameter of the microjet. It has been experimentallyshown that this difference in pressures cannot be greater than 20 timesthe surface tension γ1 divided by the outside radius of the microjet.

[0098] Therefore, given some inside and outside diameters of themicrojet, there is a range of operating pressures between a minimum anda maximum; nonetheless, experimentally the best results are obtained forpressures in the order of two to three times the minimum.

[0099] The viscosity values of the liquids must be such that the liquidwith the greater viscosity μ_(max) verifies, for a diameter d of the jetpredicted for this liquid and a difference through the orifice ΔP, theinequality: $\mu_{\max} \leq \frac{\Delta \quad {Pd}^{2}D}{Q}$

[0100] With this, the pressure gradients can overcome the extensionalforces of viscous resistance exerted by the liquid when it is suctionedtoward the orifice.

[0101] Moreover, the liquids must have very similar densities in orderto achieve the concentricity of the nucleus of the microsphere, sincethe relation of velocities between the liquids moves according to thesquare root of the densities v1/v2=(ρ2/ρ1)^(½) and both jets, the insidejet and the outside jet, must assume the most symmetrical configurationpossible, which does not occur if the liquids have different velocities(FIG. 2). Nonetheless, it has been experimentally demonstrated that, onaccount of the surface tension γ2 between the two liquids, the nucleustends to migrate toward the center of the microsphere, within prescribedparameters.

[0102] When two liquids and gas are used on the outside, the distancebetween the planes of the mouths of the concentric tubes can vary,without the characteristics of the jet being substantially altered,provided that the internal tube 31 is not introduced into the externalone 32 more than one diameter of the external tube 32 and provided thatthe internal tube 31 does not project more than two diameters from theexternal tube 32. The best results are obtained when the internal tube31 projects from the external one 32 a distance substantially the sameas the diameter of the internal tube 31. This same criterion is valid ifmore than two tubes are used, with the tube that is surrounded (innertube) projecting beyond the tube that surrounds (outer tube) by adistance substantially the same as the diameter of the first tube.

[0103] The distance between the plane of the internal tube 31 (the onethat will normally project more) and the plane of the orifice may varybetween zero and three outside diameters of the external tube 32,depending on the surface tensions between the liquids and with the gas,and on their viscosity values. Typically, the optimal distance is foundexperimentally for each particular configuration and each set of liquidsused.

[0104] The proposed atomizing system obviously requires fluids that aregoing to be used in the resulting spray to have certain flow parameters.Accordingly, flows for this use must be:

[0105] Flows that are suitable so that the system falls within theparametric window of stability. Multiplexing (i.e. several sets ofconcentric tubes) may be used, if the flows required are greater thanthose of an individual cell.

[0106] Flows that are suitable so that the mass relation of the fluidsfalls within the specifications of each application. Of course, agreater flow of gas may be supplied externally by any means in specificapplications, since this does not interfere with the functioning of theatomizer.

[0107] If the flows are varied, the characteristic time of thisvariation must be less than the hydrodynamic residence times of liquidand gas in the microjet, and less than the inverse of the first naturaloscillation frequency of the drop formed at the end of the injectionneedle.

[0108] Therefore, any means for continuous supply of gas (compressors,pressure deposits, etc.) and of liquid (volumetric pumps, pressurebottles) may be used. If multiplexing is desired, the flow of liquidmust be as homogeneous as possible between the various cells, which mayrequire impulse through multiple capillary needles, porous media, or anyother medium capable of distributing a homogeneous flow among differentfeeding points.

[0109] Each atomizing device will consist of concentric tubes 31, 32with a diameter ranging between 0.05 and 2 mm, preferably between 0.1and 0.4 mm, on which the drop from which the microjet emanates can beanchored, and a small orifice (between 0.001 and 2 mm in diameter,preferably between 0.1 and 0.25 mm), facing the drop and separated fromthe point of feeding by a distance between 0.001 and 2 mm, preferablybetween 0.2 and 0.5 mm. The orifice puts the suction gas that surroundsthe drop, at higher pressure, in touch with the area in which theatomizing is to be attained, at lower pressure.

EMBODIMENT OF FIG. 3

[0110] The embodiments of FIGS. 1 and 2 are similar in a number of ways.Both have a feeding piece which is preferably in the form of a feedingneedle with a circular exit opening. Further, both have an exit port inthe pressure chamber which is positioned directly in front of the flowpath of fluid out of the feeding source. Precisely maintaining thealignment of the flow path of the feeding source with the exit port ofthe pressure chamber can present an engineering challenge particularlywhen the device includes a number of feeding needles. The embodiment ofFIG. 3 is designed to simplify the manner in which components arealigned. The embodiment of FIG. 3 uses a planar feeding piece (which byvirtue of the withdrawal effect produced by the pressure differenceacross a small opening through which fluid is passed) to obtain multiplemicrojets which are expelled through multiple exit ports of a pressurechamber thereby obtaining multiple aerosol streams. Although a singleplanar feeding member as shown in FIG. 3 it, of course, is possible toproduce a device with a plurality of planar feeding members where eachplanar feeding member feeds fluid to a linear array of outlet orificesin the surrounding pressure chamber. In addition, the feeding memberneed not be strictly planar, and may be a curved feeding devicecomprised of two surfaces that maintain approximately the same spatialdistance between the two pieces of the feeding source. Such curveddevices may have any level of curvature, e.g. circular, semicircular,elliptical, hemi-elliptical, etc.

[0111] The components of the embodiment of FIG. 3 are as follows:

[0112]41. Feeding piece.

[0113]42. End of the feeding piece used to insert the fluid to beatomized.

[0114]43. Pressure chamber.

[0115]44. Orifice used as gas inlet.

[0116]45. End of the feeding needle used to evacuate the liquid to beatomized.

[0117]46. Orifices through which withdrawal takes place.

[0118]47. Atomizate (spray) or aerosol.

[0119]48. first fluid containing material to be atomized.

[0120]49. second fluid for creation of microjet.

[0121]50. wall of the propulsion chamber facing the edge of the feedingpiece.

[0122]51. channels for guidance of fluid through feeding piece.

[0123] d_(i)=diameter of the microjet formed; ρ_(A)=liquid density offirst fluid (48); ρ_(B)=liquid density of second fluid (49);ν_(A)=velocity of the first liquid (48); ν_(B)=velocity of the secondliquid (49); e=axial length of the orifice through which withdrawaltakes place; H=distance from the feeding needle to the microjet outlet;P₀=pressure inside the chamber;

[0124] Δp_(g)=change in pressure of the gas; P_(α)=atmospheric pressure;Q=volumetric flow rate

[0125] The proposed dispersing device consists of a feeding piece 41which creates a planar feeding channel through which a where a firstfluid 48 flows. The flow is preferably directed through one or morechannels of uniform bores that are constructed on the planar surface ofthe feeding piece 41. A pressure chamber 43 that holds the propellingflow of a second liquid 49, houses the feeding piece 41 and is under apressure above maintained outside the chamber wall 50. One or moreorifices, openings or slots (outlets) 46 made in the wall 52 of thepropulsion chamber face the edge of the feeding piece. Preferably, eachbore or channel of the feeding piece 41 has its flow path substantiallyaligned with an outlet 46.

[0126] Formation of the microjet and its acceleration are based on theabrupt pressure drop resulting from the steep acceleration undergone bythe second fluid 49 on passing through the orifice 46, similarly to theprocedure described above for embodiments of FIGS. 1 and 2 when thesecond fluid 49 is a gas.

[0127] When the second fluid 49 is a gas and the first fluid 48 is aliquid, the microthread formed is quite long and the liquid velocity ismuch smaller than the gas velocity. In fact, the low viscosity of thegas allows the liquid to flow at a much lower velocity; as a result, themicrojet is actually produced and accelerated by stress forces normal tothe liquid surface, i.e. pressure forces. Hence, one effectiveapproximation to the phenomenon is to assume that the pressuredifference established will result in the same kinetic energy per unitvolume for both fluids (liquid and gas), provided gas compressibilityeffects are neglected. The diameter d_(j) of the microjet formed from aliquid density ρ₁ that passes at a volumetric flow-rate Q through anorifice across which a pressure difference ΔP_(g) exists will be givenby$d_{j} \cong {\left( \frac{8\quad \rho_{l}}{\pi^{2}\Delta \quad P_{g}} \right)^{\frac{1}{4}}Q^{\frac{1}{2}}}$

[0128] See Gañán-Calvo, Physical Review Letters, 80:285-288 (1998).

[0129] The relation between the diameter of the microjet, d_(j), andthat of the resulting drops, {overscore (d)}, depends on the ratiobetween viscous forces and surface tension forces on the liquid on theone hand, and between dynamic forces and surface tension forces on thegas on the other (i.e. on the Ohnesorge and Weber numbers, respectively)(Hinds (Aerosol Technology, John & Sons, 1982), Lefevre (Atomization andSprays, Hemisphere Pub. Corp., 1989) and Bayvel & Orzechowski (LiquidAtomization, Taylor & Francis, 1993)). At moderate to low gas velocitiesand low viscosities the relation is roughly identical with that forcapillarity instability developed by Rayleigh:

{overscore (d)}=1.89d _(j)

[0130] Because the liquid microjet is very long, at high liquidflow-rates the theoretical rupture point lies in the turbulent zonecreated by the gas jet, so turbulent fluctuations in the gas destabilizeor rupture the liquid microjet in a more or less uneven manner. As aresult, the benefits of drop size uniformity are lost.

[0131] On the other hand, when the second fluid 49 is a liquid and thefirst fluid 48 is a gas, the facts that the liquid is much more viscousand that the gas is much less dense virtually equalize the fluid and gasvelocities. The gas microthread formed is much shorter; however, becauseits rupture zone is almost invariably located in a laminar flowingstream, dispersion in the size of the microbubbles formed is almostalways small. At a volumetric gas flow-rate Q_(g) and a liquidoverpressure ΔP₁, the diameter of the gas microjet is given by$d_{j} \cong {\left( \frac{8\quad \rho_{l}}{\pi^{2}\Delta \quad P_{l}} \right)^{\frac{1}{4}}Q_{g}^{\frac{1}{2}}}$

[0132] The low liquid velocity and the absence of relative velocitiesbetween the liquid and gas lead to the Rayleigh relation between thediameters of the microthread and those of the bubbles (i.e.d=1.89d_(j)).

[0133] If both fluids 48, 49 are liquid and scarcely viscous, then theirrelative velocities will be given by$\frac{v_{A}}{v_{B}} = \left( \frac{\rho_{B}}{\rho_{A}} \right)^{\frac{1}{2}}$

[0134] The diameter of a microjet of the first liquid at a volumetricflow-rate of A Q_(A) and an overpressure of BΔP_(B) will be given by$d_{j} \cong {\left( \frac{8\quad \rho_{A}}{\pi^{2}\Delta \quad P_{B}} \right)^{\frac{1}{4}}Q_{A}^{\frac{1}{2}}}$

[0135] At viscosities such that the velocities of both fluids 48, 49will rapidly equilibrate in the microjet, the diameter of the microjetof the first liquid will be given by$d_{j} \cong {\left( \frac{8\quad \rho_{B}}{\pi^{2}\Delta \quad P_{B}} \right)^{\frac{1}{4}}Q_{A}^{\frac{1}{2}}}$

[0136] The proposed atomization system obviously requires delivery ofthe fluids 48, 49 to be used in the dispersion process at appropriateflow-rates. Thus:

[0137] (1) Both flow-rates should be adjusted for the system so thatthey lie within the stable parameter window.

[0138] (2) The mass ratio between the flows should be compatible withthe specifications of each application. Obviously, the gas flow-rate canbe increased by using an external means in special applications (e.g.burning, drug inhalation) since this need not interfere with theatomizer operation.

[0139] (3) If the flow-rates are altered, the characteristic time forthe variation should be shorter than the hydrodynamic residence timesfor the liquid and gas in the microjet, and smaller than the reciprocalof the first natural oscillation frequency of the drop formed at the endof the feeding piece.

[0140] (4) Therefore, the gas and liquid can be dispensed by any type ofcontinuous delivery system (e.g. a compressor or a pressurized tank theformer and a volumetric pump or a pressurized bottle the latter).

[0141] (5) The atomizer can be made from a variety of materials (metal,polymers, ceramics, glass).

DRUG DELIVERY DEVICE

[0142] A device of the invention may be used to provide particles fordrug delivery, e.g. the pulmonary delivery of aerosolized pharmaceuticalcompositions. The device would produce aerosolized particles ofpharmaceutically active drug for delivery to a patient by inhalation.The device is comprised of a liquid feeding source such as a channel towhich formulation is added at one end and expelled through an exitopening. The feeding channel is surrounded by a pressurized chamber intowhich gas is fed and out of which gas is expelled from an opening. Theopening from which the gas is expelled is positioned directly in frontof the flow path of liquid expelled from the feeding channel. Variousparameters are adjusted so that pressurized gas surrounds liquid flowingout of the feeding channel in a manner so as to maintain a stablecapillary microjet of liquid until the liquid exits the pressure chamberopening and is aerosolized. The aerosolized particles having a uniformdiameter in the range of about 1 to 5 microns are inhaled into apatient's lungs and thereafter reach the patient's circulatory system.

PRODUCTION OF DRY PARTICLES

[0143] The method of the invention is also applicable in the massproduction of dry particles. Such particles are useful in providing ahighly dispersible dry pharmaceutical particles containing a drugsuitable for pulmonary delivery. The particles formed of pharmaceuticalare particularly useful in a dry powder inhaler due to the small size ofthe particles (e.g. 1, 2, 3, 4, or 5 microns in diameter) and conformityof size (e.g. 3 to 30% difference in diameter) from particle toparticle. Such particles should improve dosage by providing accurate andprecise amounts of dispersible particles to a patient in need oftreatment. Dry particles are also useful because they may serve as aparticle size standard in numerous applications.

[0144] For the formation of dry particles, the first fluid is preferablya liquid, and the second fluid is preferably a gas, although two liquidsmay also be used provided they are generally immiscible. Atomizedparticles within a desired size range (e.g., 1 micron to about 5microns) The first fluid liquid is preferably a solution containing ahigh concentration of solute. Alternatively, the first fluid liquid is asuspension containing a high concentration of suspended matter. Ineither case, the liquid quickly evaporates upon atomization (due to thesmall size of the particles formed) to leave very small dry particles.

FUEL INJECTION APPARATUS

[0145] The device of the invention is useful to introduce fuel intointernal combustion engines by functioning as a fuel injection nozzle,which introduces a fine spray of aerosolized fuel into the combustionchamber of the engine. The fuel injection nozzle has a unique fueldelivery system with a pressure chamber and a fuel source. Atomized fuelparticles within a desired size range (e.g., 5 micron to about 500microns, and preferably between 10 and 100 microns) are produced from aliquid fuel formulation provided via a fuel supply opening. The fuel maybe provided in any desired manner, e.g., forced through a channel of afeeding needle and expelled out of an exit opening of the needle.Simultaneously, a second fluid contained in a pressure chamber whichsurrounds at least the area where the formulation is provided, e.g.,surrounds the exit opening of the needle, is forced out of an openingpositioned in front of the flow path of the provided fuel, e.g. in frontof the fuel expelled from the feeding needle. Various parameters areadjusted to obtain a stable fuel-fluid interface and a stable capillarymicrojet of the fuel, which allows formation of atomized fuel particleson exiting the opening of the pressurized chamber.

[0146] Fuel injectors of the invention have three significant advantagesover prior injectors. First, fuel never contacts the periphery of theexit orifice from which it is emitted because the fuel stream issurrounded by a gas (e.g. air) which flows into the exit orifice. Thus,clogging of the orifice is eliminated or substantially reduced. Second,the fuel exits the orifice and forms very small particles which aresubstantially uniform in size, thereby allowing faster and morecontrolled combustion of the fuel. Third, by using the methods describedherein, the amount of energy needed to produce aerosolized particles offuel is substantially less than that required by other methods.

MICROFABRICATION

[0147] Molecular assembly presents a ‘bottom-up’ approach to thefabrication of objects specified with incredible precision. Molecularassembly includes construction of objects using tiny assemblycomponents, which can be arranged using techniques such as microscopy,e.g. scanning electron microspray. Molecular self-assembly is a relatedstrategy in chemical synthesis, with the potential of generatingnonbiological structures with dimensions as small as 1 to 100nanometers, and having molecular weights of 10⁴ to 10¹⁰ daltons.Microelectro-deposition and microetching can also be used inmicrofabrication of objects having distinct, patterned surfaces.

[0148] Atomized particles within a desired size range (e.g., 0.001micron to about 0.5 microns) can be produced to serve as assemblycomponents to serve as building blocks for the microfabrication ofobjects, or may serve as templates for the self-assembly of monolayersfor microassembly of objects. In addition, the method of the inventioncan employ an atomizate to etch configurations and/or patterns onto thesurface of an object by removing a selected portion of the surface.

AERATION OF WATER

[0149] More fish die from a lack of oxygen than any other cause. Fishexposed to low oxygen conditions become much more vulnerable to disease,parasites and infection, since low oxygen levels will (1) lower theoxidation/reduction potential (ORP) (2) favor growth of disease causingpathogens and (3) disrupt the function of many commercially availablebiofilters. Moreover, stress will reduce the fish activity level, growthrate, and may interfere with proper development. A continuous healthyminimum of oxygen is approximately a 6 parts per million (ppm)oxygen:water ratio, which is approximately 24 grams of dissolved oxygenper 1000 gallons of water. Fish consume on average 18 grams of oxygenper hour for every ten pounds of fish. Low level stress and poor feedingresponse can be seen at oxygen levels of 4-5 ppm. Acute stress, nofeeding and inactivity can be seen at oxygen levels of 2-4 ppm, andoxygen levels of approximately 1-2 ppm generally result in death. Thesenumbers are merely a guideline since a number of variable (e.g., watertemperature, water quality, condition of fish, level of other gasses,etc.) all may impact on actual oxygen needs.

[0150] Proper aeration depends primarily on two factors: the gentlenessand direction of water flow and the size and amount of the air bubbles.With respect to the latter, smaller air bubbles are preferable becausethey (1) increase the surface are between the air and the water,providing a larger area for oxygen diffusion and (2) smaller bubblesstay suspended in water longer, providing a greater time period overwhich the oxygen may diffuse into the water.

[0151] The technology of the invention provides a method for aeratingwater for the proper growth and maintenance of fish. A device of theinvention for such a use would provide an oxygenated gas, preferablyair, as the first fluid, and a liquid, preferably water, as the secondfluid. The air provided in a feeding source will be focused by the flowof the surrounding water, creating a stable cusp at the interface of thetwo fluids. The particles containing the gas nucleus, and preferably airnucleus, are expelled into the liquid medium where aeration is desired.When the first fluid of the invention is a liquid, and the second fluidis a gas, the inertia of the first fluid is low, and the gas abruptlydecelerates very soon after it issues from the cusp of the attacheddroplet. In such an instance, the microjet is so short that it is almostindistinguishable from the stable cusp.

SPECTROGRAPHIC ANALYSIS

[0152] An embodiment of the type shown in FIG. 1 can be modified toprovide an analytical device. A signal emitter (e.g. infrared) ispositioned such that the signal is directed at and through the stablecapillary microjet of fluid coming from the feeding source 1. A signalreceiving component is positioned opposite the emitter. Thus, the flowstream out of the feeding needle 1 is positioned directly between theemitter and receiver. Two feeding needles may be used so that one canprovide a flow stream of, for example, the solvent in which the materialto be analyzed is dissolved. Two readings are made simultaneously andthe reading of the solvent is subtracted away by microprocessor devicesof the type known to those skilled in the art to obtain a true analysisof only the material of interest.

[0153] In addition to analysis of any compound dissolved or suspended ina solvent the methodology can be used to analyze materials such as bodyfluids e.g. blood or urine. The methodology can be adapted to work in awide range of different systems, e.g. see U.S. Pat. No. 5,126,022 issuedJun. 30, 1992 and patents and publications cited therein. The presentinvention does not need to use electrical fields to move chargedmolecules as is required by many other systems. Thus, non-polarmolecules can be moved, via the present invention, through the capillarymicrojet. Because of the manner in which the stable capillary microjetis formed and maintained materials such as large proteins, nucleotidesequences, cells, and other biomaterials are not destroyed by physicalstresses.

EXAMPLES

[0154] The following examples are put forth so as to provide those ofordinary skill in the art with a complete disclosure and description ofhow to make and use the present invention, and are not intended to limitthe scope of what the inventors regard as their invention nor are theyintended to represent that the experiments below are all or the onlyexperiments performed. Efforts have been made to ensure accuracy withrespect to numbers used (e.g. amounts, temperature, etc.) but someexperimental errors and deviations should be accounted for. Unlessindicated otherwise, parts are parts by weight, molecular weight isweight average molecular weight, temperature is in degrees Centigrade,and pressure is at or near atmospheric.

[0155] The properties of sixteen different liquids are provided in Table1 TABLE 1 Liquids used and some of their physical properties at 24.5° C.(ρ: kg/m³, μ: cpoise, γ: N/m). Also given, the symbols used in theplots. Liquid ρ μ γ Symbol Heptane 684 0.38 0.021 ∘ Tap Water 1000 1.000.056 ⋄ Water + glycerol 90/10 v/v 1026 1.39 0.069 Δ Water + glycerol80/20 v/v 1052 1.98 0.068 ∇ Isopropyl alcohol 755.5 2.18 0.021 x Water +glycerol 70/30 v/v 1078 2.76 0.067  Water + glycerol 60/40 v/v 11044.37 0.067  Water + glycerol 50/50 v/v 1030 6.17 0.066 ∘ 1-Octanol 8277.47 0.024 ⋄ Water + glycerol 40/60 v/v 1156 12.3 0.065 Δ Water +glycerol 35/65 v/v 1167 15.9 0.064 ∇ Water + glycerol 30/70 v/v 118224.3 0.064 x Water glycerol 25/75 v/v 1195 38.7 0.063 + Propylene glycol1026 41.8 0.036 

[0156] The liquids of Table 1 were forced through a feeding needle ofthe type shown in FIG. 1. The end 5 of the feeding needle had aninternal radius R_(o). The exit orifice 6 had a diameter D and the wallof the pressure chamber 3 had a thickness of L. Three different deviceswere tested having the following dimensions: (D=0.15, 0.2, and 0.3 mm;L=0.1, 0.2 and 0.35 mm; R_(o)+0.2, 0.4, and 0.6 mm, respectively), andseveral distances H from the tube mouth to the orifice ranging fromH=0.5 mm to H=1.5 mm have been used. The jet diameter was measured atthe hole exit and was plotted as a function of the pressure differenceΔP_(g) and flow rate Q respectively. Although this technique allows forjet diameters even below one micron, larger flow rates and diametershave been used in this study to diminish the measuring errors.

[0157] In order to collapse all of the data, we define a reference flowrate Q_(o) and diameter d_(o) based on the minimal values, fromexpressions (3) and (5), that can be attained in stable regime for agiven ΔP_(g): $\begin{matrix}{{Q_{o} = \left( \frac{\gamma^{4}}{\rho_{1}\Delta \quad P_{g}^{3}} \right)^{\frac{1}{2}}},{d_{o} = \frac{\gamma}{\Delta \quad P_{g}}}} & (6)\end{matrix}$

[0158] These definitions provide the advantage of a nondimensionalexpression for (5), as

d _(j) /d _(o)=(8/π²)^(¼)(Q,Q_(o))^(½,)  (7

[0159] which allows for a check for the validity of neglecting thesurface tension term in (4) (i.e., Q/Q_(o) should be large).

[0160] Notice that if the measured d_(j) follows expression (5), thesurface tension cancels out in (7). Also notice that d_(j)/d_(o)≅We/2.

[0161] 350 measured values of d_(j)/d_(o) versus Q/Q_(o) are plotted inFIG. 5. A continuous line represents the theoretical prediction (7),independent of liquid viscosity and surface tension. The use ofdifferent hole and tube diameters as well as tube-hole distances doesnot have any appreciable influence on d_(j). The collapse of theexperimental data and the agreement with the simple theoretical model isexcellent. Finally, the experimental values of Q are at least four timeslarge than Q_(o) (being in most cases several hundreds times larger),which justifies the neglect of the surface tension term in Eq. (4).

[0162] While the present invention has been described with reference tothe specific embodiments thereof, it should be understood by thoseskilled in the art that various changes may be made and equivalents maybe substituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processstep or steps, to the objective, spirit and scope of the presentinvention. All such modifications are intended to be within the scope ofthe claims appended hereto.

What is claimed is:
 1. A monodispersion of bubbles of a gas in a firstliquid, the bubbles characterized by having the same diameter with adeviation in diameter from one particle to another in a range of fromabout ±3% to about ±30%.
 2. The monodispersion of bubbles as claimed inclaim 1 , wherein the deviation in diameter from one bubble to anotheris in a range of from about ±3% to ±10%.
 3. The monodispersion ofbubbles of claim 1 , wherein the monodispersion comprises more than onethousand bubbles.
 4. The monodispersion of bubbles of claim 1 , whereinthe bubbles have a diameter in a range of from about 0.1 micron to about100 microns.
 5. The monodispersion of claim 1 , wherein the gas isselected from the group consisting of air and oxygen and the liquid isaqueous.
 6. The monodispersion of claim 1 , wherein the gas iscontaminated with a toxin which toxin is soluble in the liquid.
 7. Themonodispersion of claim 6 wherein the liquid is aqueous.
 8. Themonodispersion of claim 7 , wherein the aqueous liquid is sewage.
 9. Themonodispersion of claim 1 , wherein the bubbles are created by a flowstream of gas from a source through a second liquid in a pressurechamber wherein the second liquid is forced out of an exit orifice ofthe pressure chamber while surrounding and focusing the flow stream ofgas into the first liquid where the focused flow stream of gas breaks upto form the bubbles.
 10. The monodispersion of claim 9 , wherein thefirst and second fluids are aqueous.
 11. A method of diffusing moleculesof a gas into a liquid, comprising the steps of: forcing a gas from asource opening into a first liquid in a manner so as to create a flowstream of the gas through the first liquid wherein the gas is comprisedof molecules to be diffused into a second liquid; moving the firstliquid, in a pressure chamber surrounding the source opening, out of anexit orifice in the pressure chamber wherein the flow stream of the gasflows out the exit orifice into the second liquid wherein the flowstream breaks up forming bubbles of the gas in the second liquid; andallowing molecules in the gas bubbles to diffuse into the second liquid.12. The method of claim 11 , wherein the bubbles have a size in a rangeof from about 0.1 micron to about 100 microns.
 13. The method of claim11 , wherein the bubbles are characterized by having substantially thesame diameter with a deviation in diameter from one particle to anotherin a range of from about ±3% to about ±30%.
 14. The method of claim 11 ,wherein the bubbles are emitted at regularly spaced intervals from theexit orifice of the pressure chamber.
 15. The method of claim 14 ,wherein the bubbles have a diameter in a range of from about 1 micron toabout 20 microns and are comprised of a gas selected from the groupconsisting of air and oxygen.
 16. A device for creating aerosolizedparticles, comprising: a first means for providing a first fluidcomprising a first fluid entrance port and a first fluid exit port; apressure chamber for providing a pressurized fluid to an areasurrounding the first fluid exit port, the pressure chamber comprising asecond fluid entrance port and a second fluid exit port; wherein thefirst means for providing the first fluid is a feeding needle having acylindrical channel therein whereby the first fluid entrance port andfirst fluid exit port are each circular; and wherein the feeding needleexit port has a diameter in the range of from about 0.002 to about 2 mm,and the pressure chamber exit port has a diameter in the range of about0.002 mm to about 2 mm.
 17. The device of claim 16 , wherein the feedingneedle exit port has a diameter in the range of from about 0.01 mm toabout 0.4 mm and the pressure chamber exit port has a diameter in therange of about 0.01 mm to about 0.25 mm.
 18. The device of claim 16 ,having inserted therein a first fluid having a dynamic viscosity in therange of from about 10⁻⁴ to about 1 kg/m/sec.
 19. The device of claim 16, wherein the liquid has a viscosity in a range of from about 0.3×10⁻³to about 5×10⁻² kg/m/sec; and wherein the liquid is forced through thechannel at a rate in a range of about 0.01 nl/sec to about 100 μl/secand further wherein the gas is forced through the opening of thepressure chamber at a rate in the range of from about 50 m/sec to about2000 m/sec.
 20. The device of claim 16 , wherein the liquid is forcedthrough the channel at a rate in a range of about 1 nl/sec to about 10μl/sec and further wherein the gas is forced through the opening of thepressure chamber at a rate in the range of from about 100 to 500 m/sec.